CN107050012A - A kind of licoflavone microsponge acted on whitening spot-removing and its preparation method and application - Google Patents
A kind of licoflavone microsponge acted on whitening spot-removing and its preparation method and application Download PDFInfo
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- CN107050012A CN107050012A CN201710437561.1A CN201710437561A CN107050012A CN 107050012 A CN107050012 A CN 107050012A CN 201710437561 A CN201710437561 A CN 201710437561A CN 107050012 A CN107050012 A CN 107050012A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
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Abstract
The invention discloses a kind of licoflavone microsponge acted on whitening spot-removing and its preparation method and application, prepared, comprised the following steps using class emulsion solvent diffusion method：1. take emulsifying agent to add distilled water, stir as foreign minister；2. at 60 DEG C ± 5 DEG C, in the pore-foaming agent that licoflavone and polymer are dissolved in, it is used as interior phase；3. interior phase is added in foreign minister while hot, stirring forms class emulsion；4. microsponge is separated by filtration, is washed, dries, produces.The present invention improves the hold-up of licoflavone in skin by combining microsponge technology, delivery evaluation in vivo is carried out using dialysis, zoopery is carried out in body pharmacodynamic evaluation, it was found that microsponge can extend the action time of licoflavone, local concentration of the licoflavone in skin is improved, slow release long-acting is reached, strengthens the effect of licoflavone whitening spot-removing, it can be applied to prepare the cosmetics or medicine acted on whitening spot-removing, foundation provided to study the preparation of sustained-release synergistic of big constituents.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, it is related to a kind of new pharmaceutical carrier being combined with big constituents, especially
It is licoflavone microsponge and its preparation method and application.
Background technology
Licoflavone is that a kind of flavones ingredient separated is extracted from radix glycyrrhizae, with liver protecting, anti-oxidant, anti-
The pharmacological actions such as ulcer, antitumor, anti-inflammatory antiallergic action and enzyme level.The enzyme level that research shows licoflavone and had is made
The activity for suppressing tyrosinase with being mainly reflected in, and then suppress the synthesis of melanin, it suppresses the effect of tyrosinase activity
It is 25 times of kojic acid, is ascorbic 80 times.Licoflavone can also suppress the activity of dopachrome interconvertible enzyme and hinder 5,6-
The polymerization of dihydroxy indole, therefore the product rich in licoflavone achieves good therapeutic effect in treatment chloasma.This
Outside, also there are some researches show in licoflavone liquiritin, glycyrrhizin, isoliquiritin have certain inhibitory action to aldose reductase.
At present, many natural herb cosmetics prepared by raw material of licoflavone occur commercially, but because radix glycyrrhizae is yellow
The characteristics of ketone dissolubility is poor, therefore the effect of simple external application licoflavone is unsatisfactory.
The content of the invention
It is an object of the invention to provide a kind of licoflavone microsponge acted on whitening spot-removing, by percutaneous dosing,
Drug treating time can be extended, the local biologic availability of medicine is improved, the effect such as safe efficient, long-acting is reached, and can
It is further applicable to medicine and cosmetic field.
It is a further object to provide the preparation method of above-mentioned licoflavone microsponge.
A further object of the invention is to be applied to prepare by above-mentioned licoflavone microsponge to have whitening spot-removing effect
Cosmetics or medicine.
The object of the present invention is achieved like this：A kind of preparation side of the licoflavone microsponge acted on whitening spot-removing
Method, is prepared, it is characterised in that comprise the following steps using class emulsion solvent diffusion method：1. calculate by weight, weigh 1~
8 parts of emulsifying agent, the distilled water of 100 parts of addition, stirs, and stands, is used as foreign minister；2. at 60 DEG C ± 5 DEG C, by 1~8 part
Licoflavone and 1~3 part of polymer be dissolved in 10~40 parts of pore-foaming agent, be used as interior phase；3. in 2. step is prepared
Step is mutually added to while hot 1. in obtained foreign minister, stirring forms class emulsion, continuing stirring makes pore-foaming agent volatilize；4. it is separated by filtration
Microsponge, with distillation water washing, dries, produces.
Described emulsifying agent is selected from polyvinyl alcohol.
Described polymer is selected from ethyl cellulose or triethyl citrate.
Described pore-foaming agent is selected from one or two kinds of mixing of dichloromethane, ethanol.
The step 3. in, mixing speed be 500~2500rpm, mixing time be 1~5h.
The step 4. in, be separated by filtration microsponge, first plus distillation appropriate amount of water stand overnight, thoroughly precipitation after, abandon supernatant
Liquid, then add distillation water washing, filtering；Drying mode is air drying, and the time is 12~48h.
The licoflavone microsponge as made from above-mentioned preparation method.
The licoflavone microsponge is applied to prepare the cosmetics or medicine acted on whitening spot-removing.
The formulation of the cosmetics or medicine is emulsifiable paste.
The preparation process of the emulsifiable paste is：2~6 parts of stearic acid and 0.5~2 part of glycerin monostearate is weighed,
60 DEG C of water-baths dissolving, it is to be dissolved completely after, add 2~8 parts of licoflavone microsponge, stirring is allowed to dissolve, and is used as oil phase；Take
Appropriate distilled water, 2~6 parts of glycerine and appropriate triethanolamine, are used as aqueous phase；Aqueous phase is slowly added in 60 DEG C of ± 5 DEG C of water-baths
Enter into oil phase, it is stirring while adding uniform, put to room temperature, licoflavone microsponge emulsifiable paste is made.
The present invention improves the hold-up of licoflavone in skin by combining microsponge technology, and body is carried out using dialysis
Outer release evaluation, zoopery is carried out in body pharmacodynamic evaluation, it is found that microsponge can extend the action time of licoflavone,
Local concentration of the licoflavone in skin is improved, slow release long-acting is reached, strengthens the effect of licoflavone whitening spot-removing, for research
The preparation of the sustained-release synergistic of big constituents provides foundation.
Brief description of the drawings
Fig. 1 is licoflavone of the present invention and the licoflavone microsponge outside drawing of embodiment 1 respectively；
Fig. 2 is the scanning electron microscope (SEM) photograph of the different amplification of the licoflavone microsponge of the embodiment of the present invention 1；
Fig. 3 is the vitro release contrast of liquiritin in licoflavone and licoflavone microsponge；
Fig. 4 is the vitro release contrast of isoliquiritin in licoflavone and licoflavone microsponge；
Fig. 5 is the vitro release contrast of glycyrrhizin in licoflavone and licoflavone microsponge；
Fig. 6 is the vitro release contrast of isoliquiritigenin in licoflavone and licoflavone microsponge；
Fig. 7 is the vitro release contrast of licochalcone A in licoflavone and licoflavone microsponge；
Fig. 8 is the vitro release contrast of glabridin in licoflavone and licoflavone microsponge；
Fig. 9 is ultraviolet induction melanism model；
Figure 10 is different group rat skin ammonia Silver stain slice maps；
Figure 11 is the influence that different pharmaceutical is expressed tyrosinase protein in rat skin, wherein：1 is blank control group, 2
It is positive controls for model group, 3,4 be licoflavone microsponge ointment group, 5：The common ointment group of licoflavone, 6：Blank is soft
Cream group.
Embodiment
The present invention is a kind of licoflavone microsponge acted on whitening spot-removing, and its preparation method uses class emulsion solvent
Prepared by diffusion method, comprise the following steps：1. calculate by weight, the emulsifying agent for weighing 1~8 part adds 100 in beaker
The distilled water of part, stirs, stands overnight, standby as foreign minister.The preferred polyvinyl alcohol of emulsifying agent (PVA1788).2. by weight
Measure part to calculate, at 60 DEG C ± 5 DEG C, 1~8 part of licoflavone and 1~3 part of polymer are dissolved in 10~40 parts of pore-foaming agent
In, it is used as interior phase.Polymer is used to strengthen the plasticity of preparation, preferred, ethyl or triethyl citrate.Pore-foaming agent is excellent
Select one or two kinds of mixing of dichloromethane, ethanol.3. the interior phase that 2. step is prepared is added to step while hot 1. obtained outer
Xiang Zhong, stirring forms class emulsion, and continuing stirring makes pore-foaming agent volatilize.It is preferred that mixing speed is 500~2500rpm, mixing time
For 1~5h.4. microsponge is separated by filtration, with distillation water washing, dries, produces.It is preferred that first add distillation appropriate amount of water to stand overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, drying mode is air drying, and the time is 12~48h.
The licoflavone microsponge as made from above-mentioned preparation method, can apply to prepare the change acted on whitening spot-removing
Cosmetic or medicine.Microsponge is to contain many holes inside one kind, and there is the polymer microballoon of many channel openings on surface, is lubricated
The compositions such as oil, aromatic, mineral oil, opacifier and medicine, can be wrapped in microsponge, be made not according to different demands
Same preparation, for skin or gastrointestinal administration, in extension pharmaceutical release time, improves stability, reduction side effect, raising biology
Larger advantage is shown in terms of availability especially local biologic availability.
The cosmetics or the formulation of medicine acted on whitening spot-removing can be emulsifiable paste.The preparation process of the emulsifiable paste is：
Weigh 2~6 parts of stearic acid and 0.5~2 part of glycerin monostearate, in 60 DEG C of ± 5 DEG C of water-baths dissolvings, it is to be dissolved completely
Afterwards, the licoflavone microsponge of 2~8 parts of addition, stirring is allowed to dissolve, and is used as oil phase；Take appropriate distilled water, 2~6 parts of glycerine
With appropriate triethanolamine, aqueous phase is used as；Aqueous phase is slowly added into oil phase in 60 DEG C of water-baths, it is stirring while adding uniform, put
To room temperature, licoflavone microsponge emulsifiable paste is made.
Below by way of specific example, the present invention is further elaborated, but the present invention is not limited thereto specific examples, all
The technology realized based on the above of the present invention belongs to the scope of the present invention.Preferred embodiments 1.
Embodiment 1
1. weigh 2.69g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to
It is swelled completely, it is standby as foreign minister；Licoflavone 3g, ethyl cellulose 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloros are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 1100rpm by phase in being prepared in methane while hot, forms class emulsion；Continue to stir
4h is mixed, dichloromethane is volatilized completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight,
Thoroughly after precipitation, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge；
2. 4.4g stearic acid and 1.0g glycerin monostearates are weighed in beaker, is dissolved in 60 DEG C of water-baths, it is to be dissolved complete
Quan Hou, adds 5.6g licoflavone microsponges, and stirring is allowed to dissolve, and is used as oil phase；Take appropriate distilled water, 4g glycerine and a small amount of
Triethanolamine, is used as aqueous phase；Aqueous phase is slowly added into oil phase in 60 DEG C of water-baths, it is stirring while adding uniform, put to room temperature,
Licoflavone microsponge emulsifiable paste is made.
Comparative example 1
5.6g licoflavone microsponges, other steps and addO-on therapy be the same as Example 1 are replaced with 3g licoflavones, are made sweet
Straw colour ketone emulsifiable paste.
Embodiment 2
1. weigh 2g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 2g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, is dissolved in 40ml dichloromethane
Interior phase, is added slowly in foreign minister, mixing speed is 1000rpm by phase in preparing while hot, forms class emulsion；Continue to stir 4h,
Dichloromethane is set to volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, thoroughly
After precipitation, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. the system of emulsifiable paste
Standby be the same as Example 1.
Embodiment 3
1. weigh 6g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 2g, triethyl citrate 1g are weighed, under 60 DEG C of water-baths, 40ml dichloromethane is dissolved in
Interior phase, is added slowly in foreign minister by phase in middle preparation while hot, and mixing speed is 1000rpm, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 4
1. weigh 2g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 3g, ethyl cellulose 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloromethane is dissolved in
Interior phase, is added slowly in foreign minister by phase in middle preparation while hot, and mixing speed is 1000rpm, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 5
1. weigh 6g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 3g, triethyl citrate 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloromethanes are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 1000rpm by phase in being prepared in alkane while hot, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 6
1. weigh 2g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 2g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, is dissolved in 40ml dichloromethane
Interior phase, is added slowly in foreign minister, mixing speed is 2000rpm by phase in preparing while hot, forms class emulsion；Continue to stir 4h,
Dichloromethane is set to volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, thoroughly
After precipitation, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. the system of emulsifiable paste
Standby be the same as Example 1.
Embodiment 7
1. weigh 6g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 2g, triethyl citrate 1g are weighed, under 60 DEG C of water-baths, 40ml dichloromethane is dissolved in
Interior phase, is added slowly in foreign minister by phase in middle preparation while hot, and mixing speed is 2000rpm, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 8
1. weigh 2g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 3g, ethyl cellulose 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloromethane is dissolved in
Interior phase, is added slowly in foreign minister by phase in middle preparation while hot, and mixing speed is 2000rpm, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 9
1. weigh 6g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 3g, triethyl citrate 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloromethanes are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 2000rpm by phase in being prepared in alkane while hot, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 10
1. weigh 0.64g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to
It is swelled completely, it is standby as foreign minister；Licoflavone 4g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, 40ml dichloromethanes are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 1500rpm by phase in being prepared in alkane while hot, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 11
1. weigh 7.36g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to
It is swelled completely, it is standby as foreign minister；Licoflavone 4g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, 40ml dichloromethanes are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 1500rpm by phase in being prepared in alkane while hot, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 12
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 0.64g, triethyl citrate 1g are weighed, under 60 DEG C of water-baths, 40ml dichloros are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 1500rpm by phase in being prepared in methane while hot, forms class emulsion；Continue to stir
4h is mixed, dichloromethane is volatilized completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight,
Thoroughly after precipitation, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Preparation be the same as Example 1.
Embodiment 13
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 3.68g, ethyl cellulose 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloros are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 1500rpm by phase in being prepared in methane while hot, forms class emulsion；Continue to stir
4h is mixed, dichloromethane is volatilized completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight,
Thoroughly after precipitation, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Preparation be the same as Example 1.
Embodiment 14
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 4g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, is dissolved in 40ml dichloromethane
Interior phase, is added slowly in foreign minister, mixing speed is 660rpm by phase in preparing while hot, forms class emulsion；Continue to stir 4h, make
Dichloromethane volatilizees completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thoroughly heavy
Behind shallow lake, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. the preparation of emulsifiable paste
Be the same as Example 1.
Embodiment 15
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 4g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, is dissolved in 40ml dichloromethane
Interior phase, is added slowly in foreign minister, mixing speed is 2340rpm by phase in preparing while hot, forms class emulsion；Continue to stir 4h,
Dichloromethane is set to volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, thoroughly
After precipitation, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. the system of emulsifiable paste
Standby be the same as Example 1.
Embodiment 16
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 4g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, is dissolved in 40ml dichloromethane
Interior phase, is added slowly in foreign minister, mixing speed is 1500rpm by phase in preparing while hot, forms class emulsion；Continue to stir 4h,
Dichloromethane is set to volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, thoroughly
After precipitation, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. the system of emulsifiable paste
Standby be the same as Example 1.
Embodiment 17
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 2g, triethyl citrate 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloromethanes are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 1500rpm by phase in being prepared in alkane while hot, forms class emulsion；Continue to stir
4h, makes dichloromethane volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thorough
After the precipitation of bottom, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste
Prepare be the same as Example 1.
Embodiment 18
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 4g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, is dissolved in 40ml dichloromethane
Interior phase, is added slowly in foreign minister, mixing speed is 1500rpm by phase in preparing while hot, forms class emulsion；Continue to stir 4h,
Ethanol is set to volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, thoroughly precipitation
Afterwards, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. emulsifiable paste prepare it is same
Embodiment 1.
Embodiment 19
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 4g, ethyl cellulose 1g are weighed, under 60 DEG C of water-baths, is dissolved in 40ml dichloromethane
Interior phase, is added slowly in foreign minister, mixing speed is 2000rpm by phase in preparing while hot, forms class emulsion；Continue to stir 4h,
Dichloromethane is set to volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, thoroughly
After precipitation, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. the system of emulsifiable paste
Standby be the same as Example 1.
Embodiment 20
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 2g, triethyl citrate 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloromethanes are dissolved in
Interior phase, is added slowly in foreign minister, mixing speed is 2000rpm by phase in being prepared in alkane while hot, forms class emulsion；Continue to stir
4h, makes ethanol volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thoroughly heavy
Behind shallow lake, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. the preparation of emulsifiable paste
Be the same as Example 1.
Embodiment 21
1. weigh 4g polyvinyl alcohol (PVA1788) to be dissolved in 100ml distilled water, stir, stand overnight, be allowed to be swelled
Completely, it is standby as foreign minister；Licoflavone 2g, ethyl cellulose 0.5g are weighed, under 60 DEG C of water-baths, 40ml dichloromethane is dissolved in
Interior phase, is added slowly in foreign minister by phase in middle preparation while hot, and mixing speed is 2000rpm, forms class emulsion；Continue to stir
4h, makes ethanol volatilize completely.Resulting suspension is transferred in beaker, appropriate distilled water is added, stands overnight, it is thoroughly heavy
Behind shallow lake, supernatant is abandoned, then adds distillation water washing, filtering, air drying 24h obtains licoflavone microsponge.2. the preparation of emulsifiable paste
Be the same as Example 1.
Experiment and interpretation of result
By each embodiment step 1. in obtained licoflavone microsponge be measured：
(1) with the yield of gravimetric detemination licoflavone microsponge, calculated according to formula 1：
M in formulamsFor the licoflavone microsponge quality finally given, MrmFor initial input amount, i.e. (ethyl cellulose
Quality+licoflavone quality of element or triethyl citrate).
(2) with the content of licoflavone in determined by ultraviolet spectrophotometry microsponge, its envelop rate is calculated according to formula 2.
In formula, MactThe quality of licoflavone in licoflavone microsponge to use determined by ultraviolet spectrophotometry,
MtheTo prepare the input amount of licoflavone during licoflavone microsponge.
(3) it is measured licoflavone microsponge particle diameter point using the laser diffraction particle size analyzers of Mastersize 2000
Cloth uniformity, particle diameter scanning range is 0.02-2000 μm, and particle diameter distribution uniformity is represented with the coefficient of dispersion, and the coefficient of dispersion (σ) is
Calculate what is obtained according to the percent by volume of particle diameter distribution, see formula 3.
WhereinThe percent by volume of particle diameter distribution is represented respectively.Experimental result is shown in Table 1,
The microsponge outward appearance and scanning electron microscope (SEM) photograph of preparation are shown in Fig. 1~Fig. 2.
The experimental result of table 1
(4) measure of licoflavone and its microsponge agent in vitro release
By licoflavone and the step of embodiment 1,1. obtained licoflavone microsponge carries out following test：
One section of bag filter of clip, is placed in boiling water and boils 2min respectively, removes air in bag, and one end is tightened with cotton rope, point
Each 5.0ml of other extracting liquorice flavones and licoflavone microsponge suspension is fitted into pretreatment bag filter, then the other end is tightened, and puts
In beaker, the physiological saline that 50ml contains 30%PEG-400 is then added, is positioned on magnetic stirring apparatus, rotating speed is
100rpm, temperature is 37 ± 0.5 DEG C, and 1ml is respectively sampled respectively at 1,2,3,4,6,8,10,12,24h, to dialysis after every sub-sampling
Liquid fluid infusion 1ml, with 0.45 μm of filtering with microporous membrane, determines the content of six main components of licoflavone.HPLC chromatogram condition
It is as follows：
Chromatographic condition
Chromatographic column：The HC-C18 posts of Agilent 5 (250mm × 4.6mm, 5 μm)；Flow velocity：1.0ml/min；Column temperature：30℃；
Sample size：10μl；Detection wavelength：300nm；Mobile phase：The phosphoric acid water of acetonitrile-methanol -0.2% (15：10：75), gradient elution is such as
Table 2 below：
The eluent gradient of table 2 elutes table
The content of six main components in licoflavone is measured according to above-mentioned " chromatographic condition ", its cumulative release is calculated
Degree, is plotted against time with Accumulation dissolution, as a result sees Fig. 3~Fig. 8.
Liquiritin, glycyrrhizin, isoliquiritigenin and licochalcone A in licoflavone are can be seen that in 8h from Fig. 3~Fig. 8
Accumulation dissolution four kinds of compositions corresponding with licoflavone microsponge in 24h Accumulation dissolution it is suitable, and radix glycyrrhizae is yellow in 10h
The accumulation of isoliquiritin, the Accumulation dissolution of glabridin two kinds of compositions corresponding with licoflavone microsponge in 24h is released in ketone
Degree of putting quite, illustrates that licoflavone microsponge can extend the action time of medicine, with certain slow releasing function.
(5) licoflavone and its microsponge emulsifiable paste are in body pharmacodynamic evaluation
Microsponge emulsifiable paste made from licoflavone emulsifiable paste made from comparative example 1 and embodiment 1 is subjected to following test：
1. rat melanism model is set up
40 female rats are randomly choosed, ultraviolet induction melanism model are set up, by 0.2ml/100g rat anesthesia agent
Amount, 2.25% yellow Jackets of intraperitoneal injection are anaesthetized, and dorsal body setae is removed after anesthesia, is put into homemade camera bellows, through ultraviolet
Irradiation, wavelength is 365nm, once a day, 2 hours every time, continues one week, and modeling is randomly divided into five groups, every group 8 after terminating.
Modeling result is shown in Fig. 9.
2. experiment packet and treatment
Experiment is divided into six groups, respectively the common ointment group of blank control group, model group, positive controls, licoflavone, sweet
Straw colour ketone microsponge ointment group and blank ointment group, every group of 8 female rats, modeling terminate afterwards from second day, and daily back is given
Once, every rat smears 1g ointment to medicine, and blank control group and model group continue two weeks without processing.After the completion of administration, abdomen
Chamber injection overdose of sodium pentobarbital is put to death, and removes hair, and the skin histology of clip medicine-feeding part is divided into two parts, and a part is used
10% formaldehyde, which is fixed, carries out histological stain, and another part is stored directly in -80 degree refrigerators, for Western Blot examinations
Test.
3. histological stain
The rat skin tissue removed is fixed through 10% formalin, routine paraffin wax section, carries out ammonia Silver stain：Section warp
Dewaxing treatment, 3~5min of distillation washing.Ammonia silver solution puts lucifuge at room temperature and contaminates 12~18h, distillation 1~2min of washing,
0.2% chlorination gold solution handles 5~10min, and distillation 1~2min of washing, 5% sodium thiosulfate solution is fixed 5min, filled
Divide washing 5min, dimethyl diaminophenazine chloride liquid is redyed.95% alcohol and absolute alcohol dehydration, dimethylbenzene are transparent, neutral gum sealing.To dyeing
Section afterwards, is taken pictures using microscope, and Image-Pro Plus6.0 softwares are analyzed image, and optical density/black is respectively adopted
Melanin content in plain cell area and optical density/section area characterized in two ways section.Each sample 30 photographs of random shooting
Piece is handled and analyzed, and the results are shown in Table 3, Figure 10.
The different group rat skin ammonia Silver stain section optical density changes of table 3 (N=8)
Note：Compared with model group, * represents P<0.05
4. tyrosinase protein expression experiment in rat skin
Take skin histology to be homogenized, then add the lysate (3ml RIPA+30 μ l PMSF) that 1ml has just been prepared, use rifle
Under piping and druming is several.Fully after cracking, 12000g is centrifuged 3-5 minutes, takes supernatant, then carries out egg using BCA protein quantifications kit
It is white quantitative；Then SDS-PAGE electrophoresis is carried out：Glue, the concentration glue with 8% separation gel and 5%.Sample-adding, electrophoresis：Concentrate glue warp
100V electrophoresis, separation gel is with 200V electrophoresis.Transferring film, is immersed in room temperature in confining liquid by film and closes 2 hours；Take the film out
It is directly placed into primary antibody (1:1000) in, 4 DEG C of reactions are stayed overnight；PBST washes film, 10min × 3 time；Film is transferred to secondary antibody (1:2000)
In, 37 DEG C of reaction 1h；PBST washes film, 10min × 4 time；Developed with chemoluminescence method (ECL).As a result Figure 11 is seen.
It can be seen from table 3, Figure 10, Figure 11 compared with blank control group, the melanin content increase of model group, tyrosine
The expression of enzyme also occurs in that up-regulation phenomenon, illustrates modeling success, and the synthesis for also demonstrating tyrosinase and melanin is closely related.
Compared with model group, after ursin or licoflavone, the phenomenon of decline, junket ammonia is presented in the melanin content in rat skin
The expression of sour enzyme has also reduced, and illustrates ursin and licoflavone to the tyrosinase in the rat skin of ultraviolet induction
There is inhibitory action, and then inhibit the synthesis of melanin, reduce the content of skin surface melanin.It is common with licoflavone
Ointment is compared, and after licoflavone microsponge ointment, the content of melanin is lower in the rat skin of the group, suppresses tyrosine
The expressional function of enzyme is stronger, illustrates licoflavone being prepared into after licoflavone microsponge, can form drug depot in skin,
The drug concentration of licoflavone in skin is improved, and then enhances the whitening function of licoflavone.And blank emulsifiable paste group junket
The expression of propylhomoserin enzyme is lower than the expression of model group, illustrates rat after modeling terminates, and there is also certain self-recovery work for itself
With.
By the Evaluation in Vivo and in Vitro to licoflavone and its microsponge preparation, it is found that microsponge can extend licoflavone
Action time, local drug concentration of the licoflavone in skin is improved, strengthens the effect of licoflavone whitening spot-removing；And it is micro-
Sponge can not only be combined with monomer component, moreover it is possible to be combined with the big constituents of Chinese medicine, and preparation method is easy, as a result stablizes, can
The application for being microsponge technology in skin targeting drug delivery system and suitability provide foundation, are also ground for the preparation of Chinese herb
Study carefully and exploitation lays the foundation.
Claims (10)
1. a kind of preparation method of the licoflavone microsponge acted on whitening spot-removing, is carried out using class emulsion solvent diffusion method
Prepare, it is characterised in that comprise the following steps：1. calculate by weight, weigh 1~8 part of emulsifying agent, add 100 parts of distillation
Water, stirs, and stands, is used as foreign minister；2. at 60 DEG C ± 5 DEG C, by 1~8 part of licoflavone and 1~3 part of polymer
In the pore-foaming agent for being dissolved in 10~40 parts, interior phase is used as；3. the interior phase that 2. step is prepared is added to step while hot 1. obtained outer
Xiang Zhong, stirring forms class emulsion, and continuing stirring makes pore-foaming agent volatilize；4. microsponge is separated by filtration, with distillation water washing, is dried,
Produce.
2. preparation method according to claim 1, it is characterised in that：Described emulsifying agent is selected from polyvinyl alcohol.
3. preparation method according to claim 1, it is characterised in that：Described polymer is selected from ethyl cellulose or citron
Triethylenetetraminehexaacetic acid ester.
4. preparation method according to claim 1, it is characterised in that：Described pore-foaming agent is selected from dichloromethane, ethanol
One or two mixing.
5. preparation method according to claim 1, it is characterised in that：The step 3. in, mixing speed be 500~
2500rpm, mixing time is 1~5h.
6. preparation method according to claim 1, it is characterised in that：The step 4. in, be separated by filtration microsponge, first plus
Distillation appropriate amount of water is stood overnight, thoroughly after precipitation, abandons supernatant, then add distillation water washing, filtering；Drying mode is dry for normal temperature
Dry, the time is 12~48h.
7. the licoflavone microsponge made from preparation method as described in claim 1-6 any claims.
8. licoflavone microsponge described in claim 7 is applied to prepare the cosmetics or medicine acted on whitening spot-removing.
9. licoflavone microsponge is applied to prepare the cosmetics or medicine acted on whitening spot-removing according to claim 8
Product, it is characterised in that：The formulation of the cosmetics or medicine is emulsifiable paste.
10. licoflavone microsponge is applied to prepare the cosmetics or medicine acted on whitening spot-removing according to claim 9
Product, it is characterised in that：The preparation process of the emulsifiable paste is：Weigh 2~6 parts of stearic acid and 0.5~2 part of glycerol monostearate
Ester, in 60 DEG C of water-baths dissolving, it is to be dissolved completely after, add 2~8 parts of licoflavone microsponge, stirring is allowed to dissolve, and is used as oil
Phase；Appropriate distilled water, 2~6 parts of glycerine and appropriate triethanolamine are taken, aqueous phase is used as；Aqueous phase is delayed in 60 DEG C of ± 5 DEG C of water-baths
Slowly it is added in oil phase, it is stirring while adding uniform, put to room temperature, licoflavone microsponge emulsifiable paste is made.
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|---|---|---|---|---|
| CN107890433A (en) * | 2017-11-08 | 2018-04-10 | 常州武城服饰有限公司 | A kind of preparation method of licoflavone composition for cosmetics |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102140144A (en) * | 2011-01-07 | 2011-08-03 | 上海奥利实业有限公司 | Production method of water-soluble licoflavone |
| CN103330678A (en) * | 2013-06-05 | 2013-10-02 | 南方医科大学 | Paeonol tiny sponge preparation and preparation method thereof |
| CN104546712A (en) * | 2014-12-26 | 2015-04-29 | 唯美度科技（北京）有限公司 | Licoflavone alcohol-in-oil preparation and preparation method thereof |
-
2017
- 2017-06-09 CN CN201710437561.1A patent/CN107050012A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102140144A (en) * | 2011-01-07 | 2011-08-03 | 上海奥利实业有限公司 | Production method of water-soluble licoflavone |
| CN103330678A (en) * | 2013-06-05 | 2013-10-02 | 南方医科大学 | Paeonol tiny sponge preparation and preparation method thereof |
| CN104546712A (en) * | 2014-12-26 | 2015-04-29 | 唯美度科技（北京）有限公司 | Licoflavone alcohol-in-oil preparation and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 付小华: "甘草黄酮对酪氨酸酶的抑制作用研究", 《中南药学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107890433A (en) * | 2017-11-08 | 2018-04-10 | 常州武城服饰有限公司 | A kind of preparation method of licoflavone composition for cosmetics |
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Application publication date: 20170818 |